Accumulating evidence supports the hypothesis that the AIDS dementia complex (ADC) is a direct effect of central nervous system (CNS) infection by HIV, at least in a subset of patients. This project will investigate the pathogenesis of HIV brain infection With respect to 1) the identification and localization of virus in brain and 2) whether neurotropic variants of the virus account for the clinical and pathological diversity of the disorder. Virus isolation, Southern blot detection of proviral DNA, in situ hybridization of nucleic acid and immunohistochemistry will be used to define the presence of virus and the regions of the brain and the cell types infected. Cell culture systems of lymphocytes, macrophages and glial cells will be used to explore in vitro correlates of neurotropism as reflected in differences in the capacity of isolates from different sources to replicate, spread and cause cytopathology. Restriction cleavage Southern blot analysis and direct nucleotide sequence analysis will then be used to examine sets of virus isolates derived From brain, cerebrospinal fluid and blood in order to examine the molecular basis of variable neurotropism.